This proposal describes a comparative investigation of the roles of glucose in compartmentalized metabolic and signaling pathways in sperm. It is hypothesized that regionalized organization of pathways allows the production of metabolic substrates and signaling effectors at the precise points where they are needed, crucial to cells largely devoid of substrate-translocating capabilities. Three Aims are proposed: 1) to define the roles of compartmentalized glucose metabolism in sperm function; 2) to characterize glucose uptake in sperm as they capacitate and attain fertilization competence; and 3) to dissect the signaling pathway(s) linking glucose uptake, metabolism, and capacitation. Preliminary data suggest that glucose has a unique signaling role in the control of capacitation. In addition, capacitation status is shown to regulate glucose uptake and the pentose phosphate pathway. Thus glucose has a novel signaling mechanism effecting the control of capacitation, and capacitation status regulates key pathways of glucose metabolism. Research and industrial applications of these studies will be appreciated immediately in an increased ability to handle the sperm of different species in vitro and to maintain their fertilization competence. In particular, the ability to propagate lines of animals with male-related defects in fertility will be enhanced. This ability is becoming increasingly important as animal transgenesis in a variety of models is utilized for research purposes and for the production of pharmaceuticals. Clinical applications of the proposed work include treatment of infertility and the development of contraceptives, important both for human medicine and species preservation. The Principal Investigator (PI) is qualified to perform these studies in that he is both a research scientist, published in this field, and a veterinarian with special interest and training in the reproductive of non-traditional species. Attaining both clinical (VMD) and research (PhD) degrees demonstrates a career interest in biomedical research, focusing on the comparative reproduction of alternative animal model systems. The CRRWH offers an integrated academic and clinical environment from which the PI can draw upon the expertise of recognized leaders in the study of reproduction. By allowing the PI to train in techniques of molecular biology, biochemistry, and gamete handling, the SERCA will function as a bridge between the PI's current postdoctoral training and a career as an independent biomedical researcher in comparative reproduction.